Canadian Study Links ART to an Increased Risk of Birth Defects

SAN FRANCISCO — Babies conceived via assisted reproductive technology are significantly more likely to have birth defects than those conceived naturally, a large Canadian study has shown.

Despite the observed increase, however, the incidence of birth defects in this population “is still relatively uncommon and should not discourage infertile couples from considering this reproductive option,” said lead investigator Dr. Darine El-Chaar at the annual meeting of the Society for Maternal-Fetal Medicine. Rather, “the risk information should become part of counseling for couples that are infertile in order to clarify the risk picture,” she noted.

Of the 61,208 births identified in the database for which information about reproductive assistance was available, 1,394 resulted from fertility treatments. For purposes of this study, “we lost some subjects in the ART [group] due to missing variables and other factors, and were left with 870 subjects, including 320 who used ovulation induction medications, 180 who underwent intrauterine insemination, and 370 who underwent in vitro fertilization,” said Dr. El-Chaar of the University of Ottawa.

In terms of patient and clinical characteristics, mothers in the ART group tended to be older, were less likely to have had a previous child, and were less likely to smoke than mothers in the non-ART group, said Dr. El-Chaar. Also, the ART mothers had a higher rate of cesarean sections and preterm births, and a higher number of multiple births—a factor that likely contributed to the higher preterm birth rate.

After adjustment for these factors using logistic regression, the statistical model showed an overall incidence of birth defects in the ART population of 2.62%, compared with 1.87% in the non-ART population, reported Dr. El-Chaar, noting that increased values fall within the 2%–3% rate of birth defects seen in the general population.

When analyzed by type of ART intervention, babies conceived via in vitro fertilization had the greatest increased risk of birth defects, at 2.97%, compared with 2.66% for intrauterine insemination and 2.19% for ovulation induction—a finding that suggests an association with the degree to which the various techniques manipulate egg and sperm, Dr. El-Chaar said.

“The highest increase in the ART group was seen in gastrointestinal birth defects, with an adjusted odds ratio of 8.86, followed by cardiovascular defects with an odds ratio of 2.27 and musculoskeletal defects with an odds ratio of 1.51,” said Dr. El-Chaar. There were no significant increases in the risks of neural tube or facial defects between the groups.

Some factors that may contribute to the increased risk of birth defects in the study population are the relatively advanced age of infertile couples, the medications used to stimulate ovulation or to maintain the luteal phase, and factors associated with the procedures themselves, such as the freezing and thawing of embryos or delayed oocyte fertilization, said Dr. El-Chaar. “Further studies are needed to clarify the contributions of these factors, infertility itself, and ART to the development of birth defects.”